Abstract
Label-free detection of rare cells in biological samples is an important and highly demanded task for clinical applications and various fields of research, such as detection of circulating tumor cells for cancer therapy and stem cells studies. Surface Plasmon Resonance (SPR) as a label-free method is a promising technology for detection of rare cells for diagnosis or research applications. Short detection depth of SPR (400 nm) provides a sensitive method with minimum interference of non-targets in the biological samples. In this work, we developed a novel microfluidic chip integrated with gold nanoslit SPR platform for highly efficient immunomagnetic capturing and detection of rare cells in human blood. Our method offers simple yet efficient detection of target cells with high purity. The approach for detection consists of two steps. Target cells are firs captured on functionalized magnetic nanoparticles (MNPs) with specific antibody I. The suspension containing the captured cells (MNPs-cells) is then introduced into a microfluidic chip integrated with a gold nanoslit film. MNPs-cells bind with the second specific antibody immobilized on the surface of the gold nanoslit and are therefore captured on the sensor active area. The cell binding on the gold nanoslit was monitored by the wavelength shift of the SPR spectrum generated by the gold nanoslits.
Highlights
Detection of rare cells is an essential technology with a wide range of applications in clinical diagnosis and stem cell research [1,2,3,4]
The overexpression of the receptor EphA2 has been reported in non-small cell lung carcinoma cells [41,42]
The results presented here highlight several advantages of double capturing method (DCM) combined with the funnel chip integrated with magnet and detection by Surface Plasmon Resonance (SPR) over some of the available technologies for rare cells detection
Summary
Detection of rare cells is an essential technology with a wide range of applications in clinical diagnosis and stem cell research [1,2,3,4]. To isolate and detect circulating tumor cells (CTCs) for clinical application, various strategies have been developed These methods take advantage of different properties of CTCs as compared to blood cells, such as expression of specific surface antigens, size and stiffness of cancer cells [5,6,7,8,9,10,11,12,13]. Surface plasmon resonance (SPR) is a label-free technology for detection of cells with the ability to observe the kinetic of the cell binding in real time. Yashunsky et al, have studied an infrared surface SPR-based technique for real time monitoring of epithelial cell-cell and cell-substrate interactions. Developing label-free methods, such as SPR, with the ability of real time monitoring of cell binding provides high-throughput screening techniques that can be very useful for application of rare cell detection
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